Abstract
Virus-specific CTL responses typically fall into reproducible hierarchies with particular epitopes eliciting either immunodominant or subdominant responses after viral challenge. The recently acquired capacity to directly enumerate naive CTL precursors (CTLps) in both mice and humans has implicated CTLp frequency as a key predictor of immune response magnitude after Ag challenge. However, recent studies have indicated that naive CTLp frequencies do not necessarily predict the size of the Agdriven response, indicating an important role for differential CTLp recruitment and/or expansion. This study characterizes the early emergence of various influenza epitope-specific CTL responses at multiple sites in C57BL/6 mice, and probes the role of Ag dose and TCR avidity in dictating immune response hierarchies. Despite large naive CTLp numbers, subdominance was found to arise largely as a consequence of the abrupt and premature cessation of CTL proliferation, at least for one epitope specificity. Investigation into the possible drivers of the poor proliferation observed for subdominant specificities showed that the immunodominance hierarchy endured irrespective of epitope abundance, and correlated with the prevalence of high-avidity T cells in both the naive and immune compartments. Our study strongly indicates that the quality, and not simply the quantity, of antiviral CTLs dictate response magnitude. The Journal of Immunology, 2014, 192: 4061-4068.
| Original language | English |
|---|---|
| Pages (from-to) | 4061-4068 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 192 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 1 May 2014 |
| Externally published | Yes |
Cite this
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The influenza virus-specific CTL immunodominance hierarchy in mice is determined by the relative frequency of high-avidity T cells. / Cukalac, Tania; Chadderton, Jesseka; Zeng, Weiguang; Cullen, Jolie G.; Kan, Wan Ting; Doherty, Peter C.; Jackson, David C.; Turner, Stephen J.; La Gruta, Nicole L.
In: Journal of Immunology, Vol. 192, No. 9, 01.05.2014, p. 4061-4068.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - The influenza virus-specific CTL immunodominance hierarchy in mice is determined by the relative frequency of high-avidity T cells
AU - Cukalac, Tania
AU - Chadderton, Jesseka
AU - Zeng, Weiguang
AU - Cullen, Jolie G.
AU - Kan, Wan Ting
AU - Doherty, Peter C.
AU - Jackson, David C.
AU - Turner, Stephen J.
AU - La Gruta, Nicole L.
PY - 2014/5/1
Y1 - 2014/5/1
N2 - Virus-specific CTL responses typically fall into reproducible hierarchies with particular epitopes eliciting either immunodominant or subdominant responses after viral challenge. The recently acquired capacity to directly enumerate naive CTL precursors (CTLps) in both mice and humans has implicated CTLp frequency as a key predictor of immune response magnitude after Ag challenge. However, recent studies have indicated that naive CTLp frequencies do not necessarily predict the size of the Agdriven response, indicating an important role for differential CTLp recruitment and/or expansion. This study characterizes the early emergence of various influenza epitope-specific CTL responses at multiple sites in C57BL/6 mice, and probes the role of Ag dose and TCR avidity in dictating immune response hierarchies. Despite large naive CTLp numbers, subdominance was found to arise largely as a consequence of the abrupt and premature cessation of CTL proliferation, at least for one epitope specificity. Investigation into the possible drivers of the poor proliferation observed for subdominant specificities showed that the immunodominance hierarchy endured irrespective of epitope abundance, and correlated with the prevalence of high-avidity T cells in both the naive and immune compartments. Our study strongly indicates that the quality, and not simply the quantity, of antiviral CTLs dictate response magnitude. The Journal of Immunology, 2014, 192: 4061-4068.
AB - Virus-specific CTL responses typically fall into reproducible hierarchies with particular epitopes eliciting either immunodominant or subdominant responses after viral challenge. The recently acquired capacity to directly enumerate naive CTL precursors (CTLps) in both mice and humans has implicated CTLp frequency as a key predictor of immune response magnitude after Ag challenge. However, recent studies have indicated that naive CTLp frequencies do not necessarily predict the size of the Agdriven response, indicating an important role for differential CTLp recruitment and/or expansion. This study characterizes the early emergence of various influenza epitope-specific CTL responses at multiple sites in C57BL/6 mice, and probes the role of Ag dose and TCR avidity in dictating immune response hierarchies. Despite large naive CTLp numbers, subdominance was found to arise largely as a consequence of the abrupt and premature cessation of CTL proliferation, at least for one epitope specificity. Investigation into the possible drivers of the poor proliferation observed for subdominant specificities showed that the immunodominance hierarchy endured irrespective of epitope abundance, and correlated with the prevalence of high-avidity T cells in both the naive and immune compartments. Our study strongly indicates that the quality, and not simply the quantity, of antiviral CTLs dictate response magnitude. The Journal of Immunology, 2014, 192: 4061-4068.
UR - http://www.scopus.com/inward/record.url?scp=84899495799&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1301403
DO - 10.4049/jimmunol.1301403
M3 - Article
VL - 192
SP - 4061
EP - 4068
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 9
ER -